Neuroendocrine Carcinoma of the Breast (NECB) is an uncommon subtype of breast cancer with significant diagnostic and therapeutic problems, requiring dedicated research and new approaches. At Protheragen, we specialize in the development of innovative diagnostics and therapeutics for rare and challenging cancers, including NECB. We offer an entire array of preclinical research services, specially designed to address the particular challenges posed by NECB.
Overview of Neuroendocrine Carcinoma of the Breast (NECB)
Neuroendocrine Carcinoma of the Breast (NECB) represents a rare type of breast cancer comprising roughly 2-5% of all breast cancer cases. It involves neuroendocrine differentiation, which can be demonstrated histologically using specific neuroendocrine markers like chromogranin and synaptophysin. NECB often displays a luminal A/B subtype, being ER and PR positive and HER2 negative. However, some cases of HER2-positive NECB and small cell carcinoma of the breast with basal-like features also exist. Like other forms of breast cancer, NECB usually presents as a hard breast lump, with or without axillary lymphadenopathy. The condition is diagnosed more frequently among elderly women, specifically in the sixth or seventh decade of life.
Fig.1 Immunohistochemical profiles of neuroendocrine carcinomas. (Bean G. R.,
et al., 2022)
Pathogenesis of Neuroendocrine Carcinoma of the Breast (NECB)
The precise pathogenesis of NECB is not well defined. One theory proposes that it could stem from neuroendocrine cells that in some form exist in the breast, despite these cells being inconsistently documented within normal breast tissue. Another theory suggests that NECB is the result of some form of divergent differentiation from breast cancer stem cells into neuroendocrine and epithelial lines. This form of reasoning holds true due to the fact that NECB is always seen as a mixed tumor containing endocrine and exocrine cells. It has been demonstrated by molecular studies that in the case of NECB, the neuroendocrine cells derive clonally from the intraductal component of the tumor. More recent genetic research on some NECB tumors found mutations in PIK3CA, members of the fibroblast growth factor receptor (FGFR) family, and an activating mutation of vascular endothelial growth factor receptor 2 (VEGFR2). These findings appear to support the idea of novel therapeutics through the development of specific therapeutic targets.
Diagnostics Development for Neuroendocrine Carcinoma of the Breast (NECB)
Immunohistochemistry
For the diagnosis of NECB, Immunohistochemistry (IHC) is indispensable. It comprises the application of antibodies to neuroendocrine markers like chromogranin and synaptophysin to check for expression necessary for marking the threshold of diagnosis for NECB. For the diagnosis of NECB, this diagnosis is supportive. The technique of IHC is applied to tissue samples retrieved by core needle biopsies or surgical specimens, enabling detection of neuroendocrine differentiation in the tumor cells.
Differential Diagnosis
Differential diagnosis is important in excluding other conditions which might mimic NECB. Other possibilities include Merkel cell carcinoma along with lymphoma, melanoma and metastatic neuroendocrine tumors. Together with a duct carcinoma in situ, the tumor has marked suggestive primary characteristics. Additional primary location exclusion can be done with imaging studies like CT scans of the chest and abdomen, SRS, or PET-CT with 68Ga-labeled somatostatin analogs.
Therapeutics Development for Neuroendocrine Carcinoma of the Breast (NECB)
- Chemotherapy
Chemotherapy continues to be one of the principal methods of therapy for NECB, particularly in the neoadjuvant and adjuvant contexts. This is due to the effectiveness it has with other breast cancer subtypes. Also promising, especially in high proliferation index tumors, are combinations of platinum compounds and etoposide, like those utilized in small-cell lung cancer. The aim of these regimens is to lessen the tumor's dimensions whilst increasing the survival rates.
- Targeted Therapy
Targeted therapies are becoming useful for the therapeutic of NECB. Some NECB tumors have mutations in PIK3CA and family members of FGFR, which may mean it's possible to use PI3K and FGFR inhibitors. Also, some cases of NECB have an activating mutation in VEGFR2, which, along with the high expression of VEGF-C, would justify exploring the use of antiangiogenic agents. These therapies are designed to interfere with specific biological processes at the cellular level that are associated with the development and progression of cancer.
- Peptide Receptor Radionuclide Therapy (PPRT)
For NECB tumors that express somatostatin receptors, PPRT has emerged as a viable therapeutic option. This therapy uses radiolabeled somatostatin analogs which attach to the somatostatin receptors on the tumor cell, irradiating the tumor specifically while sparing the surrounding healthy tissues. PPRT is effective in managing the disease and enhancing the patient's condition.
Table 1. Therapeutics of Neuroendocrine Carcinoma of the Breast (NECB).
| Therapeutics |
Drug Name |
Target |
Description |
Stage |
| Peptide Receptor Radionuclide Therapy (PPRT) |
NA |
Somatostatin Receptors |
Targeted radionuclide therapy for tumors expressing somatostatin receptors, effective in some NECB cases. |
Approved |
| Immune Checkpoint Inhibitors |
NA |
PD-L1, TMB, MSI |
Current immune checkpoint inhibitors are not effective in breast NEC due to uniformly negative biomarkers (PD-L1 expression, TMB, MSI). |
Approved |
| Anti-HER2 Therapy |
Trastuzumab, Pertuzumab |
HER2 |
Anti-HER2 therapies should be considered for the subset of HER2-positive NECB cases. |
Approved |
| Antibody-Drug Conjugates (ADCs) |
Farletuzumab and Mirvetuximab Soravtansine |
FOLR1 |
Monoclonal antibodies and ADCs targeting Folate Receptor 1 (FOLR1), with potential application in breast NECs expressing FOLR1. |
Preclinical |
| Histone Deacetylase (HDAC) Inhibitors |
NA |
H3K36Me3 |
Targeting histone deacetylase to address the loss of H3K36me3, associated with genomic instability in NECs. |
Preclinical |
| CDK4/6 Inhibitors |
Palbociclib, Ribociclib |
CDK4/6 |
Targeting the cell cycle control pathway, relevant in isolated cases of breast NEC with CCND1 gene amplification. |
Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen provides the full scope of diagnostics and therapeutics development services for NECB. Along with developing preclinical research plans, we carry out molecular profiling, biomarker discovery, drug testing, and other related activities. For the precise diagnosis of NECB, we guarantee the use of cutting-edge technologies that facilitate differential diagnostics. For targeted therapy design and development, our therapeutics development services strive to find new, promising molecular biology and pharmacology targets.
Diagnostics Development
- Karyotype Analysis Service
- Omics Analysis Service
- Biomarker Development Service
- Artificial Intelligence Service
Therapeutic Development
- Anticancer Peptide
- Gene Therapy
- Immunotherapy
- Monoclonal Antibody
- Phytotherapy
- Small Molecule Drug
- Therapeutic Cancer Vaccine
Disease Models
- Feline Organoids
- Canine Organoids
- Porcine Organoids
- Transgenic Mouse Models
- SUM149 Xenograft Models
Protheragen also offers preclinical efficacy testing of new drugs and therapeutic approaches, utilizing advanced animal models and cell lines to evaluate their safety and efficacy. Our team of experienced scientists and researchers works closely with clients to design and execute tailored preclinical studies, ensuring the highest standards of scientific rigor and accuracy. If you are interested in our services, please feel free to contact us.
References
- Bean, Gregory R., et al. "Genetic and immunohistochemical profiling of small cell and large cell neuroendocrine carcinomas of the breast." Modern Pathology 35.10 (2022): 1349-1361.
- Vranic, Semir, et al. "Potential novel therapy targets in neuroendocrine carcinomas of the breast." Clinical breast cancer 19.2 (2019): 131-136.
- Inno, Alessandro, et al. "Neuroendocrine carcinoma of the breast: current evidence and future perspectives." The oncologist 21.1 (2016): 28-32.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
